Researchers at the UC San Diego School of Medicine and the Moores UCSD Cancer Center have new evidence that a type of immune system cell thought to be part of the first line of defense against breast cancer may also help promote its spread. They have found that when these cells, known as lymphocytes, make an inflammatory protein called RANKL (RANK ligand), breast cancer is more likely to spread to the lungs.
They have also shown that blocking a cascade of cellular signals that follow RANKL's docking to its receptor (RANK) on tumor cells can halt cancer progression, or metastasis, and may be a possible target for drug therapy.
The scientists, led by first author Wei Tan, PhD, a postdoctoral fellow in the Department of Pharmacology at the UC San Diego School of Medicine and Michael Karin, PhD, professor of pharmacology in UCSD's Laboratory of Gene Regulation and Signal Transduction, say that the findings establish RANKL as a potential marker that can be used to help determine breast cancer prognosis and adds further proof to the potentially important role of inflammation in cancer development and spread. They reported their findings April 22, 2009 at the AACR 100th Annual Meeting 2009 in Denver.
According to Tan, the role of lymphocytes in breast cancer progression has been controversial for the last 20 years. Such cells are supposed to detect and eliminate cancer cells, but paradoxically, the infiltration of lymphocytes such as B cells and T cells into breast cancer is sometimes an indicator of poor prognosis, including cancer recurrence and metastasis. RANKL has been shown in previous studies to be an important inflammatory protein that can lead to bone loss by activating cells that help break down bone. Along with another protein, IKK alpha, it has been implicated both in tumor formation and metastasis.
The researchers created two types of mice that developed breast tumors. One group had lymphocytes in the tumors and expre
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| Contact: Steve Benowitz sbenowitz@ucsd.edu 619-543-6163 University of California - San Diego Source:Eurekalert |